The goal of this project is to identify a practical blood-based biomarker(s) that can be used as a screening test to determine who has Barrett's esophagus (BE) and who does not. Secondary goals of the project are to characterize germ line and tissue biomarkers associated with BE, and compare biomarkers in non-BE patients with and without GERD. Tertiary goals are to explore associations between biomarkers in blood or tissue and progression from BE to dysplasia or EAC, and to assess the stability of proteomic patterns over time. This study will be conducted among patients in the Barrett's Esophagus Registry (currently with 206 registrants) established at the National Naval Medical Center (NNMC) in Bethesda beginning in 1992 as well as a comparison group of approximately 600 matched non-BE patients endoscoped in the GI clinic at NNMC for other conditions. Blood and tissue samples will be collected as well as questionnaire data on risk factors and medications as well as GERD. Data analyses will be based primarily on laboratory testing of newly collected esophageal biopsies, brush samples, and blood samples, but secondarily will also include use of archival tissue biopsy samples. Follow-up of BE Registry patients will include standard periodic surveillance endoscopies, additional blood samples, and ascertainment of disease status (i.e., progression). To distinguish BE versus non-BE patients, we will: (i) assess predictability of BE status from serum proteomic patterns; (ii) characterize esophageal biopsies and brush samples for selected DNA alterations, RNA expression, and proteomic profiles; (iii) genotype patients for selected polymorphisms potentially associated with BE; (iv) compare blood and tissue biomarkers in non-BE patients with and without GERD; (v) explore the association of biomarkers with progression from BE to dysplasia or EAC; and (vi) assess proteomic pattern stability over time in BE patients. Recent studies in this project have (i) profiled and compared tissue RNA expression differences among BE, cardia, and normal squamous tissues in BE cases; (ii) compared serum hormones in BE cases versus noncases; and (ii) conducted a pilot study of serum proteomics in BE cases and noncases.